Several arene oxides and alkene oxides are known to react covalently with macromolecules, including nucleic acids, and to transform cells in vitro, suggesting their role as ultimate carcinogens, mutagens, and cytotoxins. We are studying the mixed-function oxidases, which convert unsaturated hydrocarbons to epoxides, and the further metabolism of arene and alkene oxides by soluble fraction glutathione S-transferases and microsomal epoxide hydrase in hepatic and extrahepatic tissues (including testis, ovary, and adrenal). The relative quantitative importance of the two pathways for epoxide metabolism is being studied in vitro in intact pulmonary cells, and in isolated perfused rat liver and rabbit lung preparations.